Polycystic Lipomembranous Osteodysplasia with Sclerosing Leukoencephalopathy

Excerpt

Clinical characteristics: Polycystic lipomembranous osteodysplasia with sclerosing leukoencephalopathy (PLOSL) is characterized by fractures (resulting from radiologically demonstrable polycystic osseous lesions), frontal lobe syndrome, and progressive presenile dementia beginning in the fourth decade. The clinical course of PLOSL can be divided into four stages:

1. 1

   The latent stage is characterized by normal early development.

2. 2

   The osseous stage (3rd decade of life) is characterized by pain and tenderness, mostly in ankles and feet, usually following strain or injury. Fractures are typically diagnosed several years later, most commonly in the bones of the extremities.

3. 3

   In the early neurologic stage (4th decade of life), a change of personality begins to develop insidiously. Affected individuals show a frontal lobe syndrome (loss of judgment, euphoria, loss of social inhibitions, disturbance of concentration, and lack of insight, libido, and motor persistence) leading to serious social issues.

4. 4

   The late neurologic stage is characterized by progressive dementia and loss of mobility.

Death usually occurs before age 50 years.

Diagnosis/testing: The diagnosis of PLOSL can be established in a proband with radiologically demonstrable polycystic osseous lesions, frontal lobe syndrome, and progressive presenile dementia beginning in the fourth decade. Identification of biallelic pathogenic variants in TYROBP or TREM2 can confirm the diagnosis if radiographic and clinical features are inconclusive.

Management: Treatment of manifestations: Treatment is symptomatic. Orthopedic surgery and/or devices may be of value in individual cases. Anti-seizure medication can be used to prevent epileptic seizures and secondary worsening of the condition.

Prevention of secondary complications: Some of the social consequences of PLOSL may be avoided if family members are informed early about the nature of the disorder.

Surveillance: Intervals for follow up of bone lesions and neurologic and psychiatric manifestations must be determined on an individual basis.

Genetic counseling: PLOSL is inherited in an autosomal recessive manner. If both parents are known to be heterozygous for a TREM2 or TYROBP pathogenic variant, each sib of an affected individual has at conception a 25% chance of being affected, a 50% chance of being an asymptomatic carrier, and a 25% chance of being unaffected and not a carrier. Carrier testing for at-risk relatives and prenatal testing for a pregnancy at increased risk are possible if the pathogenic variants in the family have been identified.